Recombinant Human CRBN Protein (His tag)

Collections: Other recombinant proteins, Recombinant proteins

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Product Overview

Host Species	Human
Accession	Q96SW2
Synonym	2610203G15Rik 2900045O07Rik AF229032 AW108261 Cereblon Crbn CRBN_HUMAN DKFZp781K0715 MGC27358 MRT2A OTTHUMP00000209555 piL Protein cereblon Protein x 0001
Description	Recombinant Human CRBN Protein (His tag) was expressed in Cell free. It is a Full length protein
Source	Cell free
AA Sequence	MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFD TSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQ LFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDF GIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLE SLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDA ETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLK IGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYV NPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGW KFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Molecular Weight	51 kDa including tags
Purity	>90% SDS-PAGE.Purified from an invitro E.coli expression system.
Endotoxin	< 1.0 EU per μg of the protein as determined by the LAL method
Formulation	Liquid Solution
Stability	The recombinant protein samples are stable for up to 12 months at -80°C
Reconstitution	See related COA
Unit Definition	For Research Use Only
Storage Buffer	Shipped at 4°C. Store at -20°C or -80°C. Avoid freeze / thaw cycle.

Target Details

Target Function	Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2 (Probable). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons. Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1. May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism.
Subcellular Location	Cytoplasm. Nucleus. Membrane; Peripheral membrane protein.
Protein Families	CRBN family
Database References	HGNC: 30185 OMIM: 607417 KEGG: hsa:51185 STRING: 9606.ENSP00000231948 UniGene: Hs.18925
Associated Diseases	Mental retardation, autosomal recessive 2A (MRT2A)
Tissue Specificity	Widely expressed. Highly expressed in brain.

Gene Functions References

mitochondrially expressed CRBN exhibited protease activity, and was induced by oxidative stress. PMID: 27417535
We sequenced CRBN-thalidomide binding region in 38 thalidomide embryopathy individuals and 136 Brazilians without congenital anomalies, and performed in silico analyses. Eight variants were identified, seven intronic and one in 3'UTR. PMID: 27751757
These findings thus contribute to a growing list of ID disorders caused by CRBN mutations, broaden the spectrum of phenotypes attributable to Autosomal-recessive non-syndromic intellectual disability (ARNS-ID)and provide new insight into genotype-phenotype correlations between CRBN mutations and the aetiology of ARNS-ID. PMID: 28143899
CRBN expression is of prognostic value in MM patients ineligible for ASCT treated with thalidomide as an immunomodulatory drug. With low expression indicating a possible suboptimal treatment outcome, measurement of CRBN expression might serve as additional prognostic tool in the personalized treatment approach. PMID: 27618360
Plasmablast differentiation, whether induced by BAFF or CD40L, is prevented by modulation of CRBN activity with CC-220, which induces degradation of the B cell differentiation factors Aiolos and Ikaros. Downregulation of these B cell differentiation processes by CC-220 modulation of CRBN provides a new therapeutic approach to treating B cell-mediated pathology in SLE. PMID: 28848067
High CRBN expression is associated with multiple myeloma. PMID: 28017969
CRBN negatively regulates TLR4 signaling via attenuation of TRAF6 and TAB2 ubiquitination. PMID: 27468689
Compared with newly diagnosed multiple myeloma, an increased prevalence of mutations in the Ras pathway genes KRAS, NRAS, and/or BRAF (72%), as well as TP53 (26%), CRBN (12%), and CRBN pathway genes (10%) was observed. PMID: 27458004
dual assay demonstrated superior Cereblon IHC measurement in MM samples compared with the single IHC assay using a published commercial rabbit polyclonal Cereblon antibody and could be used to explore the potential utility of Cereblon as a biomarker in the clinic PMID: 26186254
IRF4 and CRBN polymorphisms affect risk and response to treatment in multiple myeloma PMID: 28083618
overview of the current understanding of mechanism of action of Immunomodulatory drugs via CRBN and prospects for the development of new drugs that degrade protein of interest. PMID: 27460676
45.2 of multiple myeloma patients were CRBN(+). Among patients treated with thalidomide-based regimens, CRBN(+) patients showed a better treatment response than did CRBN-negative patients. There was no significant difference in survival outcomes between thalidomide- and bortezomib-based regimens in CRBN(+) patients. PMID: 27365142
GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4(CRBN) and degradation by the proteasome. PMID: 26990986
Structural dynamics of the cereblon ligand binding domain. PMID: 26024445
Our data are consistent with the idea that the CUL4A/B-DDB1-CRBN complex catalyses the polyubiquitination and thus controls the degradation of CLC-1 channels. PMID: 26021757
Data suggest that cereblon (CRBN) expression in peripheral blood chronic lymphocytic leukemia (CLL) cells is independent of prognostic factors and may be considered a potential biomarker. PMID: 24925210
High levels of full-length CRBN mRNA in lower risk 5q deletion patients are necessary for the efficacy of lenalidomide. PMID: 25284710
A copy number gain of CRBN gene might be responsible for developmental delay/intellectual disability. PMID: 25858704
Although abnormal CRBN function may be associated with intellectual disability disease onset, its cellular mechanism is still unclear. Here, we examine the role of CRBN in aggresome formation and cytoprotection. PMID: 26188093
Studied the protein cereblon , which has been recently indentified as a primary target of thalidomide and its C-terminal part as responsible for binding thalidomide within a domain carrying several invariant cysteine and tryptophan residues. PMID: 25569776
The study presents the crystal structure of human CRBN bound to DDB1 and the drug lenalidomide. PMID: 25108355
structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide PMID: 25043012
CRBN expression in bone marrow myeloma cells is associated with superior treatment response to lenalidomide in refractory myeloma and thalidomide/dexamethasone in new patients. CRBN is a crucial factor for the anti-MM effect of immunomodulators. PMID: 24687382
CRBN expression may provide a biomarker to predict response to Immunomodulatory drugs in patients with MM and its high expression can serve as a marker of good prognosis. PMID: 24118365
CRBN and IRF4 have been shown to be associated with response to lenalidomide in patients, these findings do not translate back to HMCLs, which could be attributable to factors present in the bone marrow microenvironment. PMID: 23992230
In the three intrinsically IMiD-resistant cell lines that clearly express detectable levels of cereblon, the absence of CRBN and DDB1 mutations suggest that potential cereblon-independent mechanisms of resistance exist PMID: 24166296
Presents a molecular model in which drug binding to cereblon results in the interaction of Ikaros and Aiolos to CRL4(CRBN) , leading to their ubiquitination, subsequent proteasomal degradation and T cell activation. PMID: 24328678
Data indicate that low cereblon (CRBN) expression can predict resistance to immunomodulatory drug (IMiD monotherapy and is a predictive biomarker for survival outcomes. PMID: 24129344
Findings suggest an approach for the treatment of mental retardation associated with cereblon nonsense mutation. PMID: 23983124
We investigated the role of CRBN in response to lenalidomide in myelodysplastic syndrome infants without chromosome 5 deletion. PMID: 23434730
We conclude that CRBN expression may be associated with the clinical efficacy of thalidomide. PMID: 23233657
These findings suggest that CRBN may modulate proteasome activity by directly interacting with the beta7 subunit. PMID: 23026050
Data show that in a cereblon-dependent fashion, lenalidomide downregulates IRF4 and SPIB, transcription factors that together prevent IFNbeta production. PMID: 22698399
CRBN is an essential requirement for immunoregulatory drugs activity and a possible biomarker for the clinical assessment of antimyeloma efficacy. PMID: 21860026
CRBN directly interacts with the alpha1 subunit of AMP-activated protein kinase (AMPK alpha1) and inhibits the activation of AMPK activation. PMID: 21232561
The results suggest that mutCRBN may cause ARNSID by disrupting the developmental regulation of BK(Ca) in brain regions that are critical for memory and learning. PMID: 20131966
A nonsense mutation causing a premature stop codon in CRBN was found in a large kindred with mild mental retardation. ATP-dependent degradation of proteins may play a role in memory and learning. PMID: 15557513
This may suggest new functions of CRBN in cell nucleolus besides its mitochondria protease activity in cytoplasm. PMID: 17380424
Nonsense mutation (R419X) CRBN disturbs the development of adult brain BK(Ca) isoforms. These changes are predicted to result in BK(Ca) channels with a higher intracellular Ca(2+) sensitivity, faster activation, and slower deactivation kinetics. PMID: 18414909

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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